title: Effects of different dosages of parathyroid hormone-related protein 1-34 on the bone metabolism of the ovariectomized rat model of osteoporosis.
abstract: Intermittent and low-dose parathyroid hormone (PTH) injection to stimulate bone formation has been used in the treatment of osteoporosis. The N-terminal fragment 1-34 of PTH is quite similar in structure and function to N-terminal PTH-related protein (PTHrP). PTH(1-34) and PTHrP also share a coreceptor, the PTH/PTHrP receptor. Therefore, some studies have suggested that PTHrP could effectively stimulate bone formation, similar to PTH. We used an ovariectomized (OVX) rat model of osteoporosis to study the effects of PTHrP(1-34) on bone metabolism by measuring bone mineral density (BMD), bone histomorphometrics, and biomechanical parameters. We found that subcutaneous injection of PTHrP(1-34) (40 or 80 μg/kg body weight every day) in OVX rats increased lumbar and femoral BMD, improved bone biomechanical properties, enhanced bone strength, and promoted bone formation. We selected 40 μg/kg as the preferred therapeutic dose of PTHrP(1-34) and investigated the effects of frequency of treatment (per 1, 2, 3, or 7 days) on bone metabolism in OVX rats. We found that injection of PTHrP(1-34) once per day or every other day significantly improved the BMD and strength of OVX rats. Serum calcium and phosphate levels in all treated rats did not vary significantly from control rats. Based on our results, intermittent low-dose PTHrP(1-34) injection promoted bone formation in OVX rats, suggesting a high potential for therapeutic use in osteoporosis patients.
authors.affiliation: Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong University, 324 Jingwu Road, Jinan 250021, China. xujin@medmail.com.cn
authors.forename: Jin
authors.initials: J
authors.lastname: Xu
authors.forename: Haiqin
authors.initials: H
authors.lastname: Rong
authors.forename: Hong
authors.initials: H
authors.lastname: Ji
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.forename: Wenwen
authors.initials: W
authors.lastname: Zhang
authors.forename: Yanling
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D015519:Bone Density; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism*; D002130:Calcium Phosphates / Q000097:blood; D019245:Compressive Strength; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000097:blood; D005260:Female; D005269:Femur / Q000187:drug effects / Q000378:metabolism; D008159:Lumbar Vertebrae / Q000187:drug effects / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects; D010024:Osteoporosis / Q000097:blood*; D010052:Ovariectomy; D044162:Parathyroid Hormone-Related Protein / Q000008:administration & dosage*; D010446:Peptide Fragments / Q000008:administration & dosage*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002130:Calcium Phosphates; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments; C054296:parathyroid hormone-related protein (1-34); D004958:Estradiol; C020243:calcium phosphate